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Blood Reviews Mar 2021Haemostasis stops bleeding at the site of vascular injury and maintains the integrity of blood vessels through clot formation. This regulated physiological process... (Review)
Review
Haemostasis stops bleeding at the site of vascular injury and maintains the integrity of blood vessels through clot formation. This regulated physiological process consists of complex interactions between endothelial cells, platelets, von Willebrand factor and coagulation factors. Haemostasis is initiated by a damaged vessel wall, followed with a rapid adhesion, activation and aggregation of platelets to the exposed subendothelial extracellular matrix. At the same time, coagulation factors aggregate on the procoagulant surface of activated platelets to consolidate the platelet plug by forming a mesh of cross-linked fibrin. Platelets and coagulation mutually influence each other and there are strong indications that, thanks to the interplay between platelets and coagulation, haemostasis is far more effective than the two processes separately. Clinically this is relevant because impaired interaction between platelets and coagulation may result in bleeding complications, while excessive platelet-coagulation interaction induces a high thrombotic risk. In this review, platelets, coagulation factors and the complex interaction between them will be discussed in detail.
Topics: Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Disease Susceptibility; Hemostasis; Humans; Platelet Activation; Platelet Aggregation; Platelet Membrane Glycoproteins; Protein Binding
PubMed: 32682574
DOI: 10.1016/j.blre.2020.100733 -
Hematology/oncology Clinics of North... Dec 2021Von Willebrand disease (VWD) is a common bleeding disorder, affecting male and female individuals equally, that often manifests in mucosal bleeding. VWD can be secondary... (Review)
Review
Von Willebrand disease (VWD) is a common bleeding disorder, affecting male and female individuals equally, that often manifests in mucosal bleeding. VWD can be secondary to a quantitative (Type 1 and Type 3) or qualitative (Type 2) defects in Von Willebrand factor (VWF). Initial testing includes VWF antigen, as well as a platelet binding assay to differentiate between qualitative and quantitative defects. Further subtyping requires additional testing and is needed to ensure appropriate treatment. Desmopressin, antifibrinolytics, hormonal treatments for heavy menstrual bleeding, and VWF concentrates are commonly used in the treatment of VWD.
Topics: Blood Platelets; Female; Humans; Male; von Willebrand Diseases; von Willebrand Factor
PubMed: 34400042
DOI: 10.1016/j.hoc.2021.07.004 -
International Journal of Environmental... Aug 2021Hypothermia in trauma patients is a common condition. It is aggravated by traumatic hemorrhage, which leads to hypovolemic shock. This hypovolemic shock results in a... (Review)
Review
Hypothermia in trauma patients is a common condition. It is aggravated by traumatic hemorrhage, which leads to hypovolemic shock. This hypovolemic shock results in a lethal triad of hypothermia, coagulopathy, and acidosis, leading to ongoing bleeding. Additionally, hypothermia in trauma patients can deepen through environmental exposure on the scene or during transport and medical procedures such as infusions and airway management. This vicious circle has a detrimental effect on the outcome of major trauma patients. This narrative review describes the main factors to consider in the co-existing condition of trauma and hypothermia from a prehospital and emergency medical perspective. Early prehospital recognition and staging of hypothermia are crucial to triage to proper care to improve survival. Treatment of hypothermia should start in an early stage, especially the prevention of further cooling in the prehospital setting and during the primary assessment. On the one hand, active rewarming is the treatment of choice of hypothermia-induced coagulation disorder in trauma patients; on the other hand, accidental or clinically induced hypothermia might improve outcomes by protecting against the effects of hypoperfusion and hypoxic injury in selected cases such as patients suffering from traumatic brain injury (TBI) or traumatic cardiac arrest.
Topics: Blood Coagulation Disorders; Heart Arrest; Hemorrhage; Humans; Hypothermia; Rewarming; Wounds and Injuries
PubMed: 34444466
DOI: 10.3390/ijerph18168719 -
Anesthesiology May 2020
Review
Topics: Animals; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Humans; Inflammation Mediators; Sepsis
PubMed: 32044801
DOI: 10.1097/ALN.0000000000003122 -
Current Problems in Cardiology Mar 2021Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) which initially occurred in the city of Wuhan, located in China's Hubei province, spread around... (Review)
Review
Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) which initially occurred in the city of Wuhan, located in China's Hubei province, spread around the world and on March 11, 2020, the World Health Organization declared the new Coronavirus disease 2019 (COVID-19) as a pandemic. The presence of comorbidities (eg, cardiovascular disease, obesity), Sepsis Induced Coagulopathy score >4, elevation of D-dimer (>6 times the normal value), C-reactive protein, troponins and other disseminated intravascular coagulation markers; is associated to a worse prognosis in hospitalized patients with severe COVD-19, reaching a hospital mortality of 42%. Initial anticoagulant treatment with low molecular weight heparin has been shown to reduce mortality by 48% at 7 days and 37% at 28 days and achieve a significant improvement in the arterial oxygen pressure/inspired fraction of O2 (PaO2/FiO2) by mitigating the formation of microthrombi and associated pulmonary coagulopathy.
Topics: Blood Coagulation Disorders; COVID-19; Global Health; Humans; Incidence; Pandemics; SARS-CoV-2; Thrombosis
PubMed: 33243440
DOI: 10.1016/j.cpcardiol.2020.100742 -
American Journal of Health-system... Feb 2022To provide an overview of current literature on the pathophysiology of sepsis, with a focus on mediators of endothelial injury and organ dysfunction. (Review)
Review
PURPOSE
To provide an overview of current literature on the pathophysiology of sepsis, with a focus on mediators of endothelial injury and organ dysfunction.
SUMMARY
Sepsis is a dysregulated response to infection that triggers cascades of interconnected systems. Sepsis has been a significant cause of mortality worldwide, and the recent viral pandemic that may produce severe sepsis and septic shock has been a major contributor to sepsis-related mortality. Understanding of the pathophysiology of sepsis has changed dramatically over the last several decades. Significant insight into the components of the inflammatory response that contribute to endothelial injury and trigger coagulation pathways has been achieved. Similarly, characterization of anti-inflammatory pathways that may lead to secondary infections and poor outcome has illustrated opportunities for improved therapies. Description of an increasing number of important mediators and pathways has occurred and may point the way to novel therapies to address immune dysregulation. Pharmacists will need a fundamental understanding of the overlapping pathways of the immune response to fully prepare for use of novel treatment options. While pharmacists typically understand coagulation cascade how to utilize anticoagulants, the issues in sepsis related coagulopathy and role of mediators such as cytokines and complement and role of activated platelets and neutrophils require a different perspective.
CONCLUSION
Pharmacists can benefit from understanding both the cellular and organ system issues in sepsis to facilitate assessment of potential therapies for risk and benefit.
Topics: Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Humans; Sepsis; Shock, Septic
PubMed: 34605875
DOI: 10.1093/ajhp/zxab380 -
Pathobiology : Journal of... 2021Coronavirus disease 2019 (COVID-19) causes a spectrum of disease; some patients develop a severe proinflammatory state which can be associated with a unique coagulopathy... (Review)
Review
Coronavirus disease 2019 (COVID-19) causes a spectrum of disease; some patients develop a severe proinflammatory state which can be associated with a unique coagulopathy and procoagulant endothelial phenotype. Initially, COVID-19 infection produces a prominent elevation of fibrinogen and D-dimer/fibrin(ogen) degradation products. This is associated with systemic hypercoagulability and frequent venous thromboembolic events. The degree of D-dimer elevation positively correlates with mortality in COVID-19 patients. COVID-19 also leads to arterial thrombotic events (including strokes and ischemic limbs) as well as microvascular thrombotic disorders (as frequently documented at autopsy in the pulmonary vascular beds). COVID-19 patients often have mild thrombocytopenia and appear to have increased platelet consumption, together with a corresponding increase in platelet production. Disseminated intravascular coagulopathy (DIC) and severe bleeding events are uncommon in COVID-19 patients. Here, we review the current state of knowledge of COVID-19 and hemostasis.
Topics: Blood Coagulation Disorders; Blood Platelets; COVID-19; Fibrin Fibrinogen Degradation Products; Humans; SARS-CoV-2; Thrombosis
PubMed: 33049751
DOI: 10.1159/000512007 -
Journal of Thrombosis and Haemostasis :... Jun 2019Trauma remains a leading cause of death worldwide, and most early preventable deaths in both the civilian and military settings are due to uncontrolled hemorrhage,... (Review)
Review
Trauma remains a leading cause of death worldwide, and most early preventable deaths in both the civilian and military settings are due to uncontrolled hemorrhage, despite paradigm advances in modern trauma care. Combined tissue injury and shock result in hemostatic failure, which has been identified as a multidimensional molecular, physiologic and clinical disorder termed trauma-induced coagulopathy (TIC). Understanding the biology of TIC is of utmost importance, as it is often responsible for uncontrolled bleeding, organ failure, thromboembolic complications, and death. Investigations have shown that TIC is characterized by multiple phenotypes of impaired hemostasis due to altered biology in clot formation and breakdown. These coagulopathies are attributable to tissue injury and shock, and encompass underlying endothelial, immune and inflammatory perturbations. Despite the recognition and identification of multiple mechanisms and mediators of TIC, and the development of targeted treatments, the mortality rates and associated morbidities due to hemorrhage after injury remain high. The purpose of this review is to examine the past and present understanding of the multiple distinct but highly integrated pathways implicated in TIC, in order to highlight the current knowledge gaps and future needs in this evolving field, with the aim of reducing morbidity and mortality after injury.
Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Endothelium; Exsanguination; Fibrinolysis; Hemorrhage; Hemostasis; Humans; Protein C; Shock, Hemorrhagic; Wounds and Injuries
PubMed: 30985957
DOI: 10.1111/jth.14450 -
Clinical Journal of the American... Jan 2022Patients with CKD display a significantly higher risk of cardiovascular and thromboembolic complications, with around half of patients with advanced CKD ultimately dying... (Review)
Review
Patients with CKD display a significantly higher risk of cardiovascular and thromboembolic complications, with around half of patients with advanced CKD ultimately dying of cardiovascular disease. Paradoxically, these patients also have a higher risk of hemorrhages, greatly complicating patient therapy. Platelets are central to hemostasis, and altered platelet function resulting in either platelet hyper- or hyporeactivity may contribute to thrombotic or hemorrhagic complications. Different molecular changes have been identified that may underlie altered platelet activity and hemostasis in CKD. In this study, we summarize the knowledge on CKD-induced aberrations in hemostasis, with a special focus on platelet abnormalities. We also discuss how prominent alterations in vascular integrity, coagulation, and red blood cell count in CKD may contribute to altered hemostasis in these patients who are high risk. Furthermore, with patients with CKD commonly receiving antiplatelet therapy to prevent secondary atherothrombotic complications, we discuss antiplatelet treatment strategies and their risk versus benefit in terms of thrombosis prevention, bleeding, and clinical outcome depending on CKD stage. This reveals a careful consideration of benefits versus risks of antiplatelet therapy in patients with CKD, balancing thrombotic versus bleeding risk. Nonetheless, despite antiplatelet therapy, patients with CKD remain at high cardiovascular risk. Thus, deep insights into altered platelet activity in CKD and underlying mechanisms are important for the optimization and development of current and novel antiplatelet treatment strategies, specifically tailored to these patients who are high risk. Ultimately, this review underlines the importance of a closer investigation of altered platelet function, hemostasis, and antiplatelet therapy in patients with CKD.
Topics: Blood Coagulation Disorders; Blood Platelets; Humans; Platelet Aggregation Inhibitors; Renal Insufficiency, Chronic
PubMed: 34750169
DOI: 10.2215/CJN.04100321 -
Journal of Thrombosis and Haemostasis :... Mar 2021Cardiopulmonary bypass (CPB) has allowed for significant surgical advancements, but accompanying risks can be significant and must be expertly managed. One of the... (Review)
Review
Cardiopulmonary bypass (CPB) has allowed for significant surgical advancements, but accompanying risks can be significant and must be expertly managed. One of the foremost risks is coagulopathic bleeding. Increasing levels of bleeding in cardiac surgical patients at the time of separation from CPB are associated with poor outcomes and mortality. CPB-associated coagulopathy is typically multifactorial and rarely due to inadequate reversal of systemic heparin alone. The components of the bypass circuit induce systemic inflammation and multiple disturbances of the coagulation and fibrinolytic systems. Anticipating coagulopathy is the first step in managing it, and specific patient and procedural risk factors have been identified as predictors of excessive bleeding. Medication management pre-procedure is critical, as patients undergoing cardiac surgery are commonly on anticoagulants or antiplatelet agents. Important adjuncts to avoid transfusion include antifibrinolytics, and perfusion practices such as red cell salvage, sequestration, and retrograde autologous priming of the bypass circuit have varying degrees of evidence supporting their use. Understanding the patient's coagulation status helps target product replacement and avoid larger volume transfusion. There is increasing recognition of the role of point-of-care viscoelastic and functional platelet testing. Common pitfalls in the management of post-CPB coagulopathy include overdosing protamine for heparin reversal, imperfect laboratory measures of thrombin generation that result in normal or near-normal laboratory results in the presence of continued bleeding, and delayed recognition of surgical bleeding. While challenging, the effective management of CPB-associated coagulopathy can significantly improve patient outcomes.
Topics: Blood Coagulation; Blood Coagulation Disorders; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Heparin; Humans
PubMed: 33251719
DOI: 10.1111/jth.15195